Three A/Alaska/77 ca recombinants of A/Ann Arbor/6/60 ca donor virus evaluated in man for level of attenuation. Each of the three were similarly and satifactorily attenuated despite having different genotypes. These observations suggest that M and NS genes of the ca donor virus are not major attenuating genes. A ts-1A2 "revertant" containing suppressor and other mutations leading to loss of ts phenotype was virulent in adult volunteers. This finding identified the ts genes of the ts-1A2 recombinants as genes responsible for attenuation. Recombinants possessing the two ts-1A2 ts genes may not be sufficiently stable genetically and loss of the ts property could have potential epidemiological significance.